Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation.
The present study was carried out to examine the chemopreventive effects of carotenoids such as fucoxanthin, lycopene and lutein as well as curcumin and its derivative, tetrahydrocurcumin (THC), on development of putative preneoplastic aberrant crypt foci (ACF) in colons of mice initiated with 1,2-dimethylhydrazine dihydrochloride (DMH). Influence on proliferation of colonic crypt epithelial cells was also assessed in terms of 5-bromo-2'-deoxyuridine (BrdU) incorporation. Five-week-old B6C3F1 male mice were divided into three groups, groups 1 and 2 being given DMH (20 mg/kg body wt, s.c.) twice a week for 3 weeks. Animals of group 1 were then treated with one of the test compounds, lycopene (0.005% and 0.0025%) or fucoxanthin (0.01%) in the drinking water and lutein (0.05%), curcumin (0.5%) or THC (0.5% and 0.2%) in the diet from weeks 5-12. Group 2 served as a carcinogen alone control and group 3 mice were given test compounds alone. All animals were killed at week 12. Numbers of ACF/mouse in the group 1 treated with fucoxanthin (47.1 +/- 13.7), lutein (42.6 +/- 19.6) or 0.5% THC (46.6 +/- 17.7) were significantly decreased as compared to the control group 2 value (63.3 +/- 19.4) (P < 0.01). Numbers of aberrant crypts (ACs)/mouse were also significantly lower after treatment with lutein (79.9 +/- 34.7) or 0.5% THC (81.8 +/- 32.5) than in the control group (115.1 +/- 37.1) (P < 0.01). BrdU labeling indices (LI) in mice treated with lutein and 0.5% THC were significantly decreased in both upper and lower half compartments of colonic crypts as compared to the controls (P < 0.05 and 0.01, respectively), especially the upper half data corresponding to reduction of ACs/mouse. The results thus suggest that fucoxanthin, lutein, and THC may have potential as chemopreventive agents against colon carcinogenesis.
Kim
J M
JM
Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Araki
S
S
Kim
D J
DJ
Park
C B
CB
Takasuka
N
N
Baba-Toriyama
H
H
Ota
T
T
Nir
Z
Z
Khachik
F
F
Shimidzu
N
N
Tanaka
Y
Y
Osawa
T
T
Uraji
T
T
Murakoshi
M
M
Nishino
H
H
Tsuda
H
H
D019813:1,2-Dimethylhydrazine; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens; D002338:Carotenoids / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D003474:Curcumin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D002338:Carotenoids; D003474:Curcumin; D019813:1,2-Dimethylhydrazine